IMPAIRED LYMPHOKINE SECRETION IN ANERGIC CD4(-CELLS LEADS TO DEFECTIVE HELP FOR B-CELL GROWTH AND DIFFERENTIATION() T)

The ability of anergic helper T cells to interact with resting B cells was examined in vitro. B cell growth and differentiation in coculture s were found to be dependent on the expression of CD40 ligand (CD40L) on the cloned T cells, and the expression of this molecule was only ma rginally blocked by the induction of anergy, In contrast, secretion of IL-3, IL-4, IL-5, and IL-6 within the cocultures was found to be sign ificantly reduced following the induction of anergy, and this correlat ed with the development of a 3- to 10-fold decrease in the ability of the T cells to induce B cell proliferation and IgG secretion, In contr ast to the B cells, the activation of the T cells in these cocultures did not result in proliferation; thus, the effects of T cell anergy ob served on the B cell responses were independent of an ability of clona l anergy to block T cell clonal expansion, In one T cell clone (E6), l ymphokine production was reduced in part because of an increased prope nsity to undergo apoptosis; nevertheless, two other clones (A.E7 and 1 6B.2) showed no reduced viability after anergy induction, Finally, the addition of rIL-2 to the anergic T cells significantly improved their helper activity relative to control cells; this was associated with a partial reversal of the IL-3, -4, and -5 production defects, Therefor e, clonal anergy can interfere with the delivery of helper lymphokines by T cells, resulting in a decreased capacity to stimulate the growth and differentiation of B cells.